This project aims to investigate synaptic drug action and synaptic transmission processes in bullfrog sympathetic ganglion. Pharmacological methods, electrophysiological techniques, and electron microscopy have been the approaches used. Studies of the functional and ultrastructural effects of hyperosmotic sucrose solution (400 mM) are now being concluded, the most important finding being that sucrose-induced transmission failure and drastic ultrastructural changes, similar to those seen in secondary degeneration, are reversible. We have also shown that Cs ion replacement of K ion in Ringer's solution causes postjunctional repetitive spike responses to a single preganglionic stimulus. The characteristics of this repetitive firing are identical to the repetitive firing previously reported for neostigmine and congeners. Similar effects of chlorothiazide are also under investigation, as well as interaction between Cs ion and chlorothiazide. In the coming year these studies will be extended along with collateral investigations of the early synaptic functional and structural changes following preganglionic denervation, and analytical biochemical determinations of acetylcholine release.